ORIGINAL ARTICLE Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients Ji Young Park & Joo-Hyun Nam & Young-Tak Kim & Yong-Man Kim & Jong-Hyeok Kim & Dae-Yeon Kim & Insuk Sohn & Shin-Wha Lee & Chang Ohk Sung & Kyu-Rae Kim Received: 18 October 2012 / Revised: 22 January 2013 / Accepted: 4 February 2013 / Published online: 17 February 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n =61) and USC (n =47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n =8,637) and from the Asan Medical Center (n =108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P=0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P= 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P=0.017) that was not found in advanced stage (P=0.588). USC was an independent prognos- tic factor for poor overall survival (hazard ratio, 6.125; P= 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also includ- ed our study results, a higher relative risk (1.92, 95 % CI 1.62– 2.27) was demonstrated in USC than in G3EC (P <0.001). In conclusion, our study reveals that USC is associated with a poorer prognosis compared with G3EC, only in patients with early stage carcinoma, suggesting that different treatment strat- egies should be considered according to the histologic type in order to improve treatment outcome. Keywords Endometrial carcinoma . Grade . Serous . Endometrioid . Prognosis Abbreviations USC Uterine serous carcinoma ECCC Endometrial clear cell carcinoma G3EC Grade 3 endometrioid carcinoma Introduction Endometrial carcinoma is the seventh most common cancer in women worldwide and the incidence has been rising due to an increasing population of obese women [1–4]. A dual- istic model of endometrial tumorigenesis and classification (type I and type II endometrial cancer) has been widely accepted [5, 6]. Type I endometrial carcinoma arises in a setting of endometrial hyperplasia associated with unop- posed estrogen stimulation and shows mainly endometrioid histology. On the other hand, type II endometrial carcinoma is associated with endometrial atrophy, is devoid of estrogen excess, and includes high-grade carcinomas with a nonen- dometrioid histology, including uterine serous carcinoma (USC), endometrial clear cell carcinoma (ECCC), and mixed types of both [5, 7, 8]. Molecular alterations are also considerably distinct between these two tumor types. Type I endometrial carcinoma involves mutations in PTEN, K-ras, β-catenin, PIK3CA, and microsatellite instability, whereas type II endometrial carcinoma frequently shows aneuploidy, J. Y. Park : C. O. Sung (*) : K.-R. Kim Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea e-mail: [email protected] J.-H. Nam : Y.-T. Kim : Y.-M. Kim : J.-H. Kim : D.-Y. Kim : S.-W. Lee Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea I. Sohn Samsung Cancer Research Institute, Seoul, Republic of Korea Virchows Arch (2013) 462:289–296 DOI 10.1007/s00428-013-1382-8

Poor Prognosis of Uterine Serous Carcinoma Compared With Grade 3 Endometrioid Carcinoma in Early Stage Patients - ProQuest

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ORIGINAL ARTICLE

Poor prognosis of uterine serous carcinoma comparedwith grade 3 endometrioid carcinoma in early stage patients

Ji Young Park & Joo-Hyun Nam & Young-Tak Kim &

Yong-Man Kim & Jong-Hyeok Kim & Dae-Yeon Kim &

Insuk Sohn & Shin-Wha Lee & Chang Ohk Sung &

Kyu-Rae Kim

Received: 18 October 2012 /Revised: 22 January 2013 /Accepted: 4 February 2013 /Published online: 17 February 2013# Springer-Verlag Berlin Heidelberg 2013

Abstract Difference in prognosis between grade 3 endome-trioid carcinoma (G3EC) of the endometrium and uterine se-rous carcinoma (USC) is controversial. In this study, we furtherevaluated the difference in prognosis, if any, between G3EC(n=61) and USC (n=47) on a total of 565 patients withendometrial cancer. In addition, meta-analysis was performedusing data from seven previous publications (n=8,637) andfrom the Asan Medical Center (n=108). Regarding the casesfrom our institution, USC tended to occur in older patients(≥65 years) than G3EC (P=0.011). Deep myometrial invasion(more than or equal to half) was more frequently identified inG3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P=0.021). Between patients with early stage G3EC and USC(stages I and II), there were no significant differences in anyclinicopathological parameter, but there was a significant dif-ference in overall survival (P=0.017) that was not found inadvanced stage (P=0.588). USC was an independent prognos-tic factor for poor overall survival (hazard ratio, 6.125; P=0.030) in early stage patients. In the meta-analysis on 5-yearsurvival in patients with early stage cancers, which also includ-ed our study results, a higher relative risk (1.92, 95 % CI 1.62–2.27) was demonstrated in USC than in G3EC (P<0.001). In

conclusion, our study reveals that USC is associated with apoorer prognosis compared with G3EC, only in patients withearly stage carcinoma, suggesting that different treatment strat-egies should be considered according to the histologic type inorder to improve treatment outcome.

Keywords Endometrial carcinoma . Grade . Serous .

Endometrioid . Prognosis

AbbreviationsUSC Uterine serous carcinomaECCC Endometrial clear cell carcinomaG3EC Grade 3 endometrioid carcinoma

Introduction

Endometrial carcinoma is the seventh most common cancerin women worldwide and the incidence has been rising dueto an increasing population of obese women [1–4]. A dual-istic model of endometrial tumorigenesis and classification(type I and type II endometrial cancer) has been widelyaccepted [5, 6]. Type I endometrial carcinoma arises in asetting of endometrial hyperplasia associated with unop-posed estrogen stimulation and shows mainly endometrioidhistology. On the other hand, type II endometrial carcinomais associated with endometrial atrophy, is devoid of estrogenexcess, and includes high-grade carcinomas with a nonen-dometrioid histology, including uterine serous carcinoma(USC), endometrial clear cell carcinoma (ECCC), andmixed types of both [5, 7, 8]. Molecular alterations are alsoconsiderably distinct between these two tumor types. Type Iendometrial carcinoma involves mutations in PTEN, K-ras,β-catenin, PIK3CA, and microsatellite instability, whereastype II endometrial carcinoma frequently shows aneuploidy,

J. Y. Park : C. O. Sung (*) :K.-R. KimDepartment of Pathology, Asan Medical Center,University of Ulsan College of Medicine,Seoul, Republic of Koreae-mail: [email protected]

J.-H. Nam :Y.-T. Kim :Y.-M. Kim : J.-H. Kim :D.-Y. Kim :S.-W. LeeDepartment of Obstetrics and Gynecology, Asan Medical Center,University of Ulsan College of Medicine,Seoul, Republic of Korea

I. SohnSamsung Cancer Research Institute, Seoul, Republic of Korea

Virchows Arch (2013) 462:289–296DOI 10.1007/s00428-013-1382-8